Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentCompleted18 and overNCI, OtherCDR0000066665
NCCTG-N9741, CAN-NCIC-CO13, CLB-89804, E-N9741, SWOG-N9741, N9741, CO13, NCT00003594

Trial Description


RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy is most effective in treating advanced colorectal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of various combination chemotherapy regimens in treating patients who have advanced, recurrent, or metastatic colorectal cancer that cannot be treated with surgery or radiation therapy.

Further Study Information


  • Compare the time to progression in patients with locally advanced, locally recurrent, or metastatic colorectal adenocarcinoma treated with combinations of oxaliplatin, fluorouracil, leucovorin calcium, and irinotecan.
  • Compare the quality of life, response rate, time to treatment failure, and overall survival in patients treated with these regimens.
  • Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG performance status (0-1 vs 2), prior adjuvant chemotherapy (yes vs no), prior immunotherapy (yes vs no), and age (under 65 vs 65 and over). Patients are randomized to one of three treatment arms.

Only arm II remains open to accrual.

  • Arm I (Saltz regimen): Patients receive irinotecan IV over 90 minutes followed by leucovorin calcium IV over 15 minutes and fluorouracil IV once a week for 4 weeks followed by 2 weeks of rest. Courses repeat every 6 weeks. (Arm I closed to accrual as of March 15, 2002.)
  • Arm II (FOLFOX4 regimen): Patients receive oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV over 2 hours plus fluorouracil IV over 22 hours on days 1 and 2. Courses repeat every 2 weeks.
  • Arm III (oxaliplatin plus irinotecan): Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 30 minutes on day 1. Courses repeat every 3 weeks. (Arm III closed to accrual as of March 15, 2002.) Treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed before treatment, during treatment (arm specific), and after completion of treatment.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 825 patients (275 per arm) have been accrued for this study thus far. Additional patients are being accrued on arm II. (Arms I and III closed to accrual as of March 15, 2002.)

Eligibility Criteria


  • Histologically or cytologically confirmed locally advanced, locally recurrent, or metastatic colorectal adenocarcinoma not curable by surgery or radiotherapy
  • Histological or cytological requirement waived in patients who developed radiological or clinical evidence of metastatic cancer after a prior surgical resection unless:
  • More than 5 years has elapsed since primary surgery OR
  • Primary cancer was stage I or II
  • Site of primary lesion must be or have been confirmed endoscopically, radiologically, or surgically to be or have been in the large bowel
  • Measurable or evaluable disease
  • No CNS metastases or carcinomatous meningitis



  • 18 and over

Performance status:

  • ECOG 0-2

Life expectancy:

  • At least 12 weeks


  • Absolute granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 9.0 g/dL (transfusion allowed)


  • Bilirubin no greater than 1.5 mg/dL
  • AST no greater than 5 times upper limit of normal (ULN)
  • Alkaline phosphatase no greater than 5 times ULN


  • Creatinine no greater than 1.5 times ULN


  • No uncontrolled hypertension
  • No unstable angina
  • No symptomatic congestive heart failure
  • No myocardial infarction within the past 6 months
  • No serious uncontrolled arrhythmia
  • No New York Heart Association class III or IV cardiac disease


  • No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  • No pleural effusion or ascites that cause respiratory compromise (grade 2 or worse dyspnea)


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No active or uncontrolled infection
  • No symptomatic sensory peripheral neuropathy
  • No known allergy to platinum compounds
  • No history of gastrointestinal bleeding unless it is determined to be acceptable by the enrolling physician
  • No other prior or concurrent malignancy within the past 3 years except nonmelanoma skin cancer, carcinoma in situ of the uterine cervix, or other resected malignant tumor with less than a 10% probability of tumor relapse within 3 years of diagnosis
  • No medical or psychiatric conditions that would preclude study
  • No colonic or small bowel disorders with uncontrolled symptoms of more than 3 loose stools per day
  • Colostomy or ileostomy allowed at investigator's discretion


Biologic therapy:

  • Prior adjuvant immunotherapy for resected stage II-IV disease allowed if adjuvant therapy concluded at least 1 year before documentation of recurrent disease
  • No concurrent sargramostim (GM-CSF)


  • No prior chemotherapy for advanced colorectal cancer
  • No prior standard adjuvant chemotherapy for rectal cancer
  • Prior adjuvant fluorouracil for resected stage II-IV disease allowed if adjuvant therapy concluded at least 1 year before documentation of recurrent disease

Endocrine therapy:

  • Not specified


  • See Disease Characteristics
  • At least 4 weeks since prior major radiotherapy (e.g., chest or bone palliative radiotherapy)
  • No prior radiotherapy to more than 15% of bone marrow
  • No prior standard adjuvant radiotherapy for rectal cancer


  • See Disease Characteristics
  • At least 4 weeks since prior major surgery (e.g., laparotomy) (2 weeks for minor surgery) and recovered
  • Insertion of a vascular access device not considered major or minor surgery


  • No other concurrent investigational agents

Trial Contact Information

Trial Lead Organizations/Sponsors

North Central Cancer Treatment Group

  • National Cancer Institute
  • Cancer and Leukemia Group B
  • NCIC-Clinical Trials Group
  • Eastern Cooperative Oncology Group
  • Southwest Oncology Group
Henry Clement Pitot, Study Chair
Roscoe F. Morton
Charles S. Fuchs, Study Chair
Brian Peter Findlay, Study Chair
Ramesh K. Ramanathan, Study Chair
Stephen K. Williamson, Study Chair

Link to the current record.
NLM Identifier NCT00003594 processed this data on May 19, 2015

Note: Information about this trial is from the database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the record to standardize the names of study sponsors, sites, and contacts. only lists sites that are recruiting patients for active trials, whereas lists all sites for all trials. Questions and comments regarding the presented information should be directed to